The purpose of this study is to evaluate the cardiovascular (CV) safety profile of omarigliptin in participants with type 2 diabetes mellitus (T2DM). The primary hypothesis is that treatment with omarigliptin 25 mg once weekly is non-inferior to treatment with placebo and active comparators across the omarigliptin program with regard to the risk of developing a confirmed event in the primary CV composite endpoint.

Change from baseline in hemoglobin A1C (A1C) at Week 18 in a sub-study of participants taking insulin (with or without metformin) (Period 1) [ Time Frame: Baseline and Week 18 ] [ Designated as safety issue: No ]

Percentage of participants who experienced at least one adverse event in a sub-study of participants taking insulin (with or without metformin) (Period 1) [ Time Frame: Up to Week 18 ] [ Designated as safety issue: Yes ]

Percentage of participants who discontinued from study drug due to an adverse event in a sub-study of participants taking insulin (with or without metformin) (Period 1) [ Time Frame: Up to Week 18 ] [ Designated as safety issue: Yes ]

Time to first event in the cardiovascular (CV) composite endpoint of CV-related death, nonfatal myocardial infarction (MI), or nonfatal stroke (Stage 2) [ Time Frame: Up to 8 years (from the first randomization date, 2012-Dec) ] [ Designated as safety issue: Yes ]

Change from baseline in A1C at 4 months [ Time Frame: Baseline and 4 months ] [ Designated as safety issue: No ]

Time to initiation of long-term insulin therapy (long-term insulin therapy is defined as a continuous period of insulin use of more than 3 months) in participants not receiving insulin at baseline [ Time Frame: Up to 8 years ] [ Designated as safety issue: No ]

Change from baseline in FPG at Week 18 in a sub-study of participants taking insulin (with or without metformin) (Period 1) [ Time Frame: Baseline and Week 18 ] [ Designated as safety issue: No ]

Percentage of participants who experienced at least one adverse event [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]

Percentage of participants who discontinued from study drug due to an adverse event [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]

Time to first event for each of the individual CV endpoints: confirmed CV-related death, MI (fatal + nonfatal), and stroke (fatal + nonfatal) (Stage 2) [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]

Time to all-cause mortality (Stage 2) [ Time Frame: Up to 8 years ] [ Designated as safety issue: Yes ]

The trial was amended to extend the length of the trial in order to meet FDA requirements for the post-approval assessment of cardiovascular (CV) safety. The trial now contains 2 time intervals: Period 1 and Period 2. Period 1 refers to the time interval up to this recent protocol amendment and Period 2, the time interval from this protocol amendment until the end of the study. Participants in Period 1 will be re-consented and continue into Period 2. If required, additional participants will be enrolled in Period 2. Stage 1 refers to the prefiling United States Food and Drug Administration (US FDA) requirement to rule out a 80% increased CV risk. Stage 2 refers to the US FDA post-marketing requirement to rule out a 30% increased CV risk. The Stage 1 assessment of CV risk occurred during Period 1 and was based on a meta-analysis of major adverse CV events (MACE) and unstable angina across the omarigliptin Phase 2/Phase 3 program. The Stage 2 assessment will be based on MACE in P018 alone including CV events from both Period 1 and Period 2.

Eligibility

Ages Eligible for Study:

40 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Diagnosed with type 2 diabetes mellitus

Is on one of the following diabetes treatment regimens that is stable for at least 12 weeks (except for pioglitazone for at least 16 weeks) and is within the associated A1C range for that treatment regimen:

A1C >= 7.0% and <=10.0% (>=53 mmol/mol and <=86 mmol/mol) on (a) monotherapy with a sulfonylurea or meglitinide OR (b) dual combination therapy with a sulfonylurea or a meglitinide and MF, PIO, AGI, or SGLT2i OR

(1) Male; (2) female not of reproductive potential; or (3) female of reproductive potential who agrees to remain abstinent or use alone or in conjunction with their partner 2 methods of contraception to prevent pregnancy during the study and for 21 days after the last dose of study drug.

On a weight loss program and is not in the maintenance phase or has been on a weight loss medication in the past 6 months or has undergone bariatric surgery within 12 months prior to study participation

Pregnant or breast feeding, or is expecting to conceive or donate eggs during the trial, including 21 days following the last dose of study drug

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01703208